Pulmonary surfactant reduces surface tension at the air-liquid interface of the alveolar lining, preventing the lungs from collapsing at end expiration. Surfactant deficiency is a common disorder in premature infants and causes respiratory distress syndrome (RDS), which can be effectively treated with natural surfactants extracted from animal lungs (Fujiwara, T. and Robertson B. (1992) In: Robertson, B., van Golde, L. M. G. and Batenburg, B. (eds) Pulmonary Surfactant: From Molecular Biology to Clinical Practice Amsterdam, Elsevier, pp. 561–592). The main constituents of these surfactant preparations are phospholipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), phosphatidylgly-cerol (PG) and the hydrophobic surfactant proteins B and C (SP-B and SP-C). The hydrophilic surfactant proteins SP-A and SP-D which are C-type (Ca2+-dependent) collagenous lectins and thought to act primarily in the host-defence system, are normally not included in the surfactant preparations due to the organic solvent extraction procedures employed.
SP-B and SP-C constitute only about 1–2% of the surfactant mass, but are still able to exercise dramatic improvements on surface activity, compared to pure lipid preparations (Curstedt, T. et al. (1987) Eur. J. Biochem. 168, 255–262; Takahashi, A., Nemoto, T. and Fujiwara, T. (1994) Acta Paediatr. Jap. 36, 613–618). The primary and secondary structures of SP-B and SP-C and a tertiary structure of SP-C in solution have been determined (see 4). SP-B is composed of two identical polypeptide chains of 79 amino acids, connected with an interchain disulphide bridge (Curstedt, T. et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2985–2989; Johansson, J., Curstedt, T. and Jörnvall, H. (1991) Biochemistry 30, 6917–6921). Each monomeric chain has three intrachain disulphide bridges and at least four amphipathic helices exhibiting one polar and one unpolar face through which SP-B may interact with two lipid bilayers and bring them into close proximity (Andersson, M. et al. (1995) FEBS Lett. 362, 328–332). SP-C is a lipoprotein composed of 35 amino acid residues with an α-helical domain between residues 9–34 (Johansson, J. et al. (1994) Biochemistry 33, 6015–6023). The helix is composed mostly of valyl-residues and is embedded in a lipid bilayer and oriented in parallel with the lipid acyl chains (Vandenbussche, et al. (1992) Eur. J. Biochem. 203, 201–209). Two palmitoyl groups are covalently linked to cysteine residues in positions 5 and 6 in the N-terminal part of the peptide (Curstedt, T. et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2985–2989). The two conserved positively charged residues, arginine and lysine, at positions 11 and 12, possibly interact with the negatively charged head groups of the lipid membrane, thus increasing its rigidity. The rigidity of the lipid-peptide interaction may be decreased towards the C-terminal end, since it contains small or hydrophobic residues only, making this part potentially more mobile in a phospholipid bilayer. SP-C is thought to influence the thickness and fluidity of the surrounding lipids via the extremely stable poly-valyl helix (Johansson, J. and Curstedt, T. (1997) Eur. J. Biochem. 244, 675–693).